NEW DELHI: Dengue is a dangerous debilitating disease that occasionally kills people and has no known cure or treatment.

Two vaccines against the dreaded disease - one foreign and one Indian - await regulatory clearances. A multi-national pharma giant seeks waiver for a large clinical trial to be done so that the vaccine can be introduced as soon as possible looking at the emergency.

A promising Indian candidate vaccine rusts on the shelf of a laboratory in Delhi even as millions suffer. So should India bite the bullet and go ahead tough and not easy choices need to be made?

But how big is the dengue problem, occasionally the authorities have behaved like ostriches. A landmark 2014 study by the government's National Institute of Health and Family Welfare (NIHFW), New Delhi, found that India could have had "an annual average of 5,778,406 clinically diagnosed dengue cases, or 282 times the reported number per year" between 2006-2012.

In 2013, an assessment by a team of 18 researchers from seven countries, published in the British journal Nature, said "India alone contributed 22-44 million dengue infections" in the world - which suggested that the Ministry's estimate could be lower by a 1,000 times.

"The government numbers are just the tip of the iceberg," said Dr Soumya Swaminathan, Director General of the Indian Council of Medical Research (ICMR).

She added that nobody really knew the real burden of dengue, and the truth lay somewhere between the 282-times-more and the 1,000-times-more estimates. It is for this reason that the country desperately needs a vaccine against dengue.

It is a bite from the blood sucking tiger mosquito that causes dengue, India has been fighting a losing battle against this disease. There are at least two vaccines in the pipeline that can help.

Globally the most advanced is a vaccine made by pharma giant Sanofi and recommended by the WHO that is only effective in the age group 9 years to 45 as a tool to tackle dengue.

Earlier this year the Indian health ministry rejected the introduction of the Sanofi dengue vaccine to India as the company wanted fast track introduction and sought a waiver of the Phase III clinical trial in India.

The Ministry of Health and Family Welfare noted that "the evidence was not sufficient to waive conducting a clinical trial in India."

In the last few weeks the company has approached the regulatory authorities to re-consider the rejection and a committee headed by clinicians from the All India Institute of Medical Sciences and Maulana Azad Medical College have suggested that the vaccine be introduced under strict post marketing surveillance. But there are hoops still to be overcome.

Jean-Pierrre Baylet, Country Head, Sanofi Pasteur India, Mumbai says, "There are at least 5 good reasons to believe in our dengue vaccines: 20 years of research including India, recommendation from the World Health Organization, 10 countries have already adopted the vaccines, high against severe dengue and 5 lakh people globally have already been vaccinated so far."

The vaccine has been extensively studied in 40,000 people in 15 different countries including India. The results of the study in India are very similar to the global results worldwide, running more clinical trials in India would delay the introduction of the vaccine by another three years and the suffering in India would continue.

According to Sanofi with 1.5 million doses of the vaccine having been distributed. Brazil and the Philippines also launched large-scale public vaccination programs designed to address the specific dengue burden in these countries.

According to Sanofi in 2015, a pooled efficacy analysis of the two Phase III study results, including 25 months of follow-up, were published in a prestigious medical journal - the New England Journal of Medicine, which showed that: 9 out of 10 vaccinated individuals (9 years of age and older) were protected against severe dengue. 8 out of 10 vaccinated individuals (9 years of age and older) were protected against hospitalisations due to dengue.

Beneficial protection against hospitalisation due to dengue and severe dengue was documented for up to 4 years post dose 1 of vaccination in the study population 9 years and older.

The Sanofi Pasteur dengue vaccine was developed without subsidies confirms the company. Adding that it was a complex vaccine to develop and manufacture, requiring more than 20 years of research and large investments to build sufficient capacities to respond to a world demand. In fact, the dengue vaccine production facility in Neuville sur Saone, France, is the largest investment ever made by Sanofi Pasteur.

Baylet says it illustrates the company's commitment to providing solutions to the unmet medical needs related to dengue. Dengue vaccine development represents one of the largest financial commitments made by Sanofi in the past decade, about 1.5 billion euros. It includes investment in production infrastructure dedicated to the dengue vaccine of around 350 million euros.

Of this amount, approximately 300 million euros were dedicated to a new vaccine production site near Lyon. In India Sanofi did a limited Phase II trial among adults aged 18-45 years across five sites -- Delhi, Ludhiana, Bengaluru, Pune and Kolkata.

Sanofi says they found the vaccine to be well tolerated and producing antibodies against all 4 dengue serotypes - which is consistent with the global trial results.

India is taking a precautionary approach on the introduction of the Sanofi dengue vaccine.

Swaminathan says, "In fact in younger children there was reverse effect which was found to increase the severity slightly. So we felt that is the scientists who evaluated it felt that it might be safe to wait for a little more data to get generated and to see its uptake and experience in other countries before we proceed in India."

But how safe is the vaccine?

Says Baylet, "We have extensive clinical data including 40,000 people in 15 different countries including India. The results of the clinical trial in India are very similar to the results of the global clinical trials worldwide. We have now 4 years of follow up on these clinical trials. We have vaccinated over more 5 lakh people. There is no issue with the vaccine."

The big question that worries many is why is it that Sanofi is first introducing the dengue vaccine in the developing world?

Baylet explains, "Typically, the industry developed the vaccines for Europe or USA and it came to the developing world much later. In case of dengue, the issue is mostly in the developing world, so our ambition was to develop the vaccines for the people who are suffering the most from the disease in the intermediate countries and we decided to develop and introduce first that vaccine in those countries where it would have the strongest impact."

Another candidate is an Indian vaccine made by a lab in Delhi which is awaiting its first human clinical trials and the search for an industry partner is delaying its further development. Reports suggest that Indian pharma giant Sun Pharma has evinced prima facie interest in partnering.

Indian scientists reported a breakthrough in 2015 and the vaccine was tested on monkeys. Scientists say it will take time to get to the human trials stage and if everything works to plan, a made-in-India dengue vaccine could be available in five years from now.

"Yes, we definitely have a working candidate vaccine for dengue with us. For me, developing a dengue vaccine for India is like putting a man on the moon, it is of that importance," Dr Navin Khanna, dengue researcher at the International Centre for Genetic Engineering and Biotechnology in New Delhi had told NDTV about this discovery.

The ICGEB plans a larger vaccine trial on monkeys in America; the full-fledged human trial after that could cost more than Rs 100 crore.

Work on the Indian dengue vaccine started five years ago with an investment of Rs 8 crore. The development was largely kept secret till the team procured an international patent.

Developing a vaccine against dengue has not proved easy as there are four different strains of the virus.

Swaminathan says, "The early results of the dengue vaccine from ICGEB look quite promising, however, it has to go through several stages of testing before it can come into human trials. The ICMR is quite keen to work with the ICGEB in taking it forward to human trials and we would be willing to invest and supporting those clinical trials."

At one point Infosys founder and now-turned philanthropist N R Narayana Murthy wanted to fund the clinical trial but then government regulations on how funds from corporate social responsibility it seems did not permit such a move and the proposal died a premature death.

An expert from WHO's India Programme office warned that "dengue is the fastest growing disease in the world and climate change will only exacerbate the problem".

As recently on July 29, the WHO recommended the use of the vaccine in endemic countries as part of a comprehensive prevention and control strategy. Hope lies in controlling the disease through the early introduction of a safe vaccine.

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